UniProt functional annotation for P35637



	UniProt functional annotation for P35637

UniProt code: P35637.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: DNA/RNA-binding protein that plays a role in various cellular processes such as transcription regulation, RNA splicing, RNA transport, DNA repair and damage response (PubMed:27731383). Binds to nascent pre-mRNAs and acts as a molecular mediator between RNA polymerase II and U1 small nuclear ribonucleoprotein thereby coupling transcription and splicing (PubMed:26124092). Binds also its own pre- mRNA and autoregulates its expression; this autoregulation mechanism is mediated by non-sense-mediated decay (PubMed:24204307). Plays a role in DNA repair mechanisms by promoting D-loop formation and homologous recombination during DNA double-strand break repair (PubMed:10567410). In neuronal cells, plays crucial roles in dendritic spine formation and stability, RNA transport, mRNA stability and synaptic homeostasis (By similarity). {ECO:0000250|UniProtKB:P56959, ECO:0000269|PubMed:10567410, ECO:0000269|PubMed:24204307, ECO:0000269|PubMed:26124092, ECO:0000269|PubMed:27731383}.

Subunit: Self-oligomerizes (via N-terminal region) (PubMed:25453086). Oligomerization is essential for chromatin binding (PubMed:25453086). Component of nuclear riboprotein complexes. Interacts with ILF3, TDRD3 and SF1 (PubMed:9660765). Interacts through its C-terminus with SFRS13A (PubMed:9774382). Interacts with OTUB1 and SARNP. Interacts with LRSAM1 (PubMed:27615052). Interacts with SAFB1 in a DNA-dependent manner; this interaction tethers FUS to chromatin (PubMed:27731383). Interacts with MATR3 (PubMed:27731383). Interacts with SNRNP70 and POLR2A; these interactions couple RNA transcription and splicing (PubMed:26124092). Interacts (through its RNA-binding domain) with RALY (through its RNA- binding domain); both are components of the same RNPs (PubMed:30354839). {ECO:0000269|PubMed:17196963, ECO:0000269|PubMed:18632687, ECO:0000269|PubMed:25453086, ECO:0000269|PubMed:26124092, ECO:0000269|PubMed:27615052, ECO:0000269|PubMed:27731383, ECO:0000269|PubMed:30354839, ECO:0000269|PubMed:9660765, ECO:0000269|PubMed:9774382}.

Subcellular location: Nucleus {ECO:0000269|PubMed:19251627, ECO:0000269|PubMed:19251628, ECO:0000269|PubMed:24204307, ECO:0000269|PubMed:25453086, ECO:0000269|PubMed:30354839}. Note=Displays a punctate pattern inside the nucleus and is excluded from nucleoli. {ECO:0000269|PubMed:25453086}.

Tissue specificity: Ubiquitous.

Ptm: Arg-216 and Arg-218 are dimethylated, probably to asymmetric dimethylarginine.

Ptm: Phosphorylated in its N-terminal serine residues upon induced DNA damage. ATM and DNA-PK are able to phosphorylate FUS N-terminal region. {ECO:0000269|PubMed:18620545, ECO:0000269|PubMed:29897835}.

Disease: Note=A chromosomal aberration involving FUS is found in a patient with malignant myxoid liposarcoma. Translocation t(12;16)(q13;p11) with DDIT3. {ECO:0000269|PubMed:7503811}.

Disease: Note=A chromosomal aberration involving FUS is a cause of acute myeloid leukemia (AML). Translocation t(16;21)(p11;q22) with ERG. {ECO:0000269|PubMed:8187069}.

Disease: Angiomatoid fibrous histiocytoma (AFH) [MIM:612160]: A distinct variant of malignant fibrous histiocytoma that typically occurs in children and adolescents and is manifest by nodular subcutaneous growth. Characteristic microscopic features include lobulated sheets of histiocyte-like cells intimately associated with areas of hemorrhage and cystic pseudovascular spaces, as well as a striking cuffing of inflammatory cells, mimicking a lymph node metastasis. {ECO:0000269|PubMed:11063792}. Note=The gene represented in this entry is involved in disease pathogenesis. A chromosomal aberration involving FUS is found in a patient with angiomatoid fibrous histiocytoma. Translocation t(12;16)(q13;p11.2) with ATF1 generates a chimeric FUS/ATF1 protein. {ECO:0000269|PubMed:11063792}.

Disease: Amyotrophic lateral sclerosis 6, with or without frontotemporal dementia (ALS6) [MIM:608030]: A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. {ECO:0000269|PubMed:19251627, ECO:0000269|PubMed:19251628, ECO:0000269|PubMed:19861302, ECO:0000269|PubMed:20124201, ECO:0000269|PubMed:27604643}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Tremor, hereditary essential 4 (ETM4) [MIM:614782]: A common movement disorder mainly characterized by postural tremor of the arms. Head, legs, trunk, voice, jaw, and facial muscles also may be involved. The condition can be aggravated by emotions, hunger, fatigue and temperature extremes, and may cause a functional disability or even incapacitation. Inheritance is autosomal dominant. {ECO:0000269|PubMed:22863194}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the RRM TET family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		DNA/RNA-binding protein that plays a role in various cellular processes such as transcription regulation, RNA splicing, RNA transport, DNA repair and damage response (PubMed:27731383). Binds to nascent pre-mRNAs and acts as a molecular mediator between RNA polymerase II and U1 small nuclear ribonucleoprotein thereby coupling transcription and splicing (PubMed:26124092). Binds also its own pre- mRNA and autoregulates its expression; this autoregulation mechanism is mediated by non-sense-mediated decay (PubMed:24204307). Plays a role in DNA repair mechanisms by promoting D-loop formation and homologous recombination during DNA double-strand break repair (PubMed:10567410). In neuronal cells, plays crucial roles in dendritic spine formation and stability, RNA transport, mRNA stability and synaptic homeostasis (By similarity). {ECO:0000250\|UniProtKB:P56959, ECO:0000269\|PubMed:10567410, ECO:0000269\|PubMed:24204307, ECO:0000269\|PubMed:26124092, ECO:0000269\|PubMed:27731383}.


Subunit:		Self-oligomerizes (via N-terminal region) (PubMed:25453086). Oligomerization is essential for chromatin binding (PubMed:25453086). Component of nuclear riboprotein complexes. Interacts with ILF3, TDRD3 and SF1 (PubMed:9660765). Interacts through its C-terminus with SFRS13A (PubMed:9774382). Interacts with OTUB1 and SARNP. Interacts with LRSAM1 (PubMed:27615052). Interacts with SAFB1 in a DNA-dependent manner; this interaction tethers FUS to chromatin (PubMed:27731383). Interacts with MATR3 (PubMed:27731383). Interacts with SNRNP70 and POLR2A; these interactions couple RNA transcription and splicing (PubMed:26124092). Interacts (through its RNA-binding domain) with RALY (through its RNA- binding domain); both are components of the same RNPs (PubMed:30354839). {ECO:0000269\|PubMed:17196963, ECO:0000269\|PubMed:18632687, ECO:0000269\|PubMed:25453086, ECO:0000269\|PubMed:26124092, ECO:0000269\|PubMed:27615052, ECO:0000269\|PubMed:27731383, ECO:0000269\|PubMed:30354839, ECO:0000269\|PubMed:9660765, ECO:0000269\|PubMed:9774382}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:19251627, ECO:0000269\|PubMed:19251628, ECO:0000269\|PubMed:24204307, ECO:0000269\|PubMed:25453086, ECO:0000269\|PubMed:30354839}. Note=Displays a punctate pattern inside the nucleus and is excluded from nucleoli. {ECO:0000269\|PubMed:25453086}.
Tissue specificity:		Ubiquitous.
Ptm:		Arg-216 and Arg-218 are dimethylated, probably to asymmetric dimethylarginine.
Ptm:		Phosphorylated in its N-terminal serine residues upon induced DNA damage. ATM and DNA-PK are able to phosphorylate FUS N-terminal region. {ECO:0000269\|PubMed:18620545, ECO:0000269\|PubMed:29897835}.
Disease:		Note=A chromosomal aberration involving FUS is found in a patient with malignant myxoid liposarcoma. Translocation t(12;16)(q13;p11) with DDIT3. {ECO:0000269\|PubMed:7503811}.
Disease:		Note=A chromosomal aberration involving FUS is a cause of acute myeloid leukemia (AML). Translocation t(16;21)(p11;q22) with ERG. {ECO:0000269\|PubMed:8187069}.
Disease:		Angiomatoid fibrous histiocytoma (AFH) [MIM:612160]: A distinct variant of malignant fibrous histiocytoma that typically occurs in children and adolescents and is manifest by nodular subcutaneous growth. Characteristic microscopic features include lobulated sheets of histiocyte-like cells intimately associated with areas of hemorrhage and cystic pseudovascular spaces, as well as a striking cuffing of inflammatory cells, mimicking a lymph node metastasis. {ECO:0000269\|PubMed:11063792}. Note=The gene represented in this entry is involved in disease pathogenesis. A chromosomal aberration involving FUS is found in a patient with angiomatoid fibrous histiocytoma. Translocation t(12;16)(q13;p11.2) with ATF1 generates a chimeric FUS/ATF1 protein. {ECO:0000269\|PubMed:11063792}.
Disease:		Amyotrophic lateral sclerosis 6, with or without frontotemporal dementia (ALS6) [MIM:608030]: A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. {ECO:0000269\|PubMed:19251627, ECO:0000269\|PubMed:19251628, ECO:0000269\|PubMed:19861302, ECO:0000269\|PubMed:20124201, ECO:0000269\|PubMed:27604643}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Tremor, hereditary essential 4 (ETM4) [MIM:614782]: A common movement disorder mainly characterized by postural tremor of the arms. Head, legs, trunk, voice, jaw, and facial muscles also may be involved. The condition can be aggravated by emotions, hunger, fatigue and temperature extremes, and may cause a functional disability or even incapacitation. Inheritance is autosomal dominant. {ECO:0000269\|PubMed:22863194}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the RRM TET family. {ECO:0000305}.